Trifluoroacetic acid → 4-chloro-5-iodo-7-(4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidine

Participants

Reaction Conditions

Reaction Steps

A mixture of tert-butyl 4-(4-chloro-5-iodo-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-1-piperidinecarboxylate (1.0 g, 2.16 mmol) in dichloromethane (10 mL) at 0° C. was treated with a cold solution of trifluoroacetic acid (20%) in dichloromethane (total volume 56 mL). Reaction stirred at 0° C. under a nitrogen atmosphere for 3 hours. The solvent was evaporated under reduced pressure at ambient temperature. Ethyl acetate (50 mL) and 5 N hydrochloric acid (50 mL) were added to the solid. The layers were partitioned, and the organic layer was extracted with 5 N hydrochloric acid (150 mL). The aqueous layers were combined, cooled to 0° C., and basified using 50% sodium hydroxide aqueous solution at 0° C. The aqueous layer was extracted with dichloromethane (300 mL). The organic layers were combined, dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The resulting product, 4-chloro-5-iodo-7-(4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidine (0.520 g, 99%) was dried 5 under high vacuum. 1H NMR (DMSO-d6, 400 MHz); 8.63(s, 1H), 8.12(s, 1H), 4.75-4.68 (m, 1H), 3.09-3.06(d, 2H, J=12 Hz), 2.70-2.60(m, 2H), 1.99-1.83(m, 4H); Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 m, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 4.022 min.

Provenance & Evidence